R24, an IgG3 mouse monoclonal antibody (mAb) raised against human melanoma, recognizes the ganglioside GD.sub.3. GD.sub.3 is abundantly expressed on most melanomas but is expressed only to a limited extent and at a low concentration on normal tissues.
R24 is a mixture of three molecular species (FIG. 11). The species have been designated V1-R24, V2-R24, and R24. In V1-R24 and V2-R24, one or both of the light chains, respectively, have been replaced by an irrelevant light chain. These molecules show very little R24-like activity. Only the third molecular species is completely intact and is the "true" R24. This implies that the GD.sub.3 -binding regions (also termed "paratopes") of V1-R24 and V2-R24 are altered as compared to R24. We developed a method of purifying R24 to isolate the three species. This method employs an ion-exchange chromatography column (Mono Q, Pharmacia, Inc.).
Phase 1 trial of R24 in melanoma patients resulted in 4 out of 21 objective responses. For these reasons, GD.sub.3 is an appealing target for immunotherapy of cancer.
Anti-idiotypic monoclonal antibodies to R24 are expected to carry the internal image of GD.sub.3. Such a monoclonal antibody is a valuable immunological reagent. GD.sub.3 is poorly immunogenic; however, we find that immunization with an R24 anti-idiotypic mAb results in an anti-GD.sub.3 immune response with high titer.
The present invention, BEC2, is an anti-idiotypic monoclonal antibody which was made against the anti-GD.sub.3 monoclonal antibody R24.